Vascular reconstruction remains a clinical dilemma for patients requiring coronary artery bypass, peripheral vascular surgery, or arteriovenous fistula. Over 1 million procedures of coronary revascularization are performed annually in the United States. Despite their utility in the absence of autologous vessel replacement, permanent prosthetic vascular graft materials present a lifetime risk of thrombosis and infection. Alternatively, tissue engineering offers an attractive option for vascular grafting, particularly for creating small-diameter (e.g., <5 mm) blood vessels by combining patient's own cells with a natural and/or synthetic vascular scaffold to yield an implantable vascular graft.
Researchers have focused on the endothelialization of the lumen of vascular scaffolds to produce an anti-thrombogenic surface. The integrity of these endothelialized vascular scaffolds, however, has been suboptimal, both physiologically and structurally compared to native arteries.
Other types of vascular scaffolds have been proposed in which an electrospun matrix allows for endothelial cell (EC) adhesion onto the luminal surface and homogenous infiltration of smooth muscle cells (SMC) into the outer layer. See, Ju, Y. M., et al., Bilayered scaffold for engineering cellularized blood vessels, Biomaterials, 2010; 31(15):4313-21. However, uniform and effective cell seeding is challenging when an electrospun matrix alone serves as the vascular scaffold.
In practice, it is difficult to achieve the architecture of an outer smooth muscle cell layer in a vascular construct using convention smooth muscle cell seeding techniques. Accordingly, there exists a need for methods of fabricating mature smooth muscle layers in vascular constructs.